Variant chr4-25664197-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006424.3(SLC34A2):c.251-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 750,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000043 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC34A2
NM_006424.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004623

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.716

Variant links:

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC34A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-25664197-T-C is Benign according to our data. Variant chr4-25664197-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 789940.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SLC34A2	NM_006424.3 linkuse as main transcript	c.251-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2 linkuse as main transcript	c.248-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001171469.2
SLC34A2	NM_001177999.2 linkuse as main transcript	c.248-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8 linkuse as main transcript	c.251-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006424.3	ENSP00000371483	P4	O95436-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

129726

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000235

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000489

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000426

AC:

AN:

750694

Hom.:

Cov.:

AF XY:

0.0000513

AC XY:

AN XY:

390220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000558

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000276

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000516

Gnomad4 OTH exome

AF:

0.0000955

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000616

AC:

AN:

129808

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

62666

show subpopulations

Gnomad4 AFR

AF:

0.0000892

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000235

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000124

Gnomad4 NFE

AF:

0.0000489

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00162

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.59

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over